Cellular apoptotic pathways prevent the propagation of inappropriate cell numbers, cell fates or faulty genetic templates which are implicated in cancer, neurodegeneration, autoimmunity, heart and renal disease. Because multiple apoptotic pathways and molecular targets that transduce the signals are present, highly specific therapeutics can be developed. Whole animal screens which permit simultaneous evaluation of drug effectiveness and toxicity are needed. In Phase I research, we propose to develop a reproducible zebrafish apoptosis assay to screen compounds of therapeutic interest. Advantages of the zebrafish model include its genetic similarity to humans, transparency, rapid embryonic development, low maintenance cost, and ease with which chemicals can be introduced into the embryo. PROPOSED COMMERCIAL APPLICATIONS: By providing a rapid method for screening drugs, the zebrafish assay will help to streamline the drug development process for diseases characterized by cell accumulation (cancer, autoimmune diseases and viral illness) as well as diseases characterized by cell death (AIDS, neurodegenerative diseases, myelodysplastic syndromes, ischemic injury and toxin induced liver disease).